Shohat M, Bu X, Shohat T, Fischel-Ghodsian N, Magal N, Nakamura Y, Schwabe A D, Schlezinger M, Danon Y, Rotter J I
Department of Medical Genetics, Beilinson Medical Center, Petah Tikva, Israel.
Am J Hum Genet. 1992 Dec;51(6):1349-54.
Familial Mediterranean fever (FMF) is a recurrent inflammatory disorder characterized by short episodes of fever, peritonitis, pleuritis, and arthritis. While FMF has been shown to be inherited in an autosomal recessive fashion in both non-Ashkenazi Jews and Armenian families, clinical differences have raised the possibility of genetic heterogeneity. As its pathogenesis is unknown, mapping of the gene for FMF may provide the first objective method for early and accurate diagnosis of this disease. After excluding 45% of the entire human genome, we studied 14 Armenian and 9 non-Ashkenazi Jewish families with FMF and tested linkage with the alpha-globin locus on chromosome 16. Analysis of the PvuII length polymorphism of the 3' HVR (hypervariable region) probe showed significant linkage with the FMF gene (maximum lod score [lodmax] = 9.76 at maximum recombination fraction [theta] = .076). In the Armenians, the lodmax = 3.61 at theta = .10; and for the non-Ashkenazi Jews, lodmax = 6.28 at theta = .06. There was no evidence for genetic heterogeneity between the Armenians and the non-Ashkenazi Jews (chi 2 = 1.28; P = .26) or within either ethnic group (chi 2 = .00; P = .50). Thus, the gene for FMF is linked to the alpha-globin complex on chromosome 16p in both non-Ashkenazi Jews and Armenians.
家族性地中海热（FMF）是一种复发性炎症性疾病，其特征为发热、腹膜炎、胸膜炎和关节炎的短暂发作。虽然已证明FMF在非阿什肯纳齐犹太人和亚美尼亚家族中以常染色体隐性方式遗传，但临床差异增加了基因异质性的可能性。由于其发病机制尚不清楚，FMF基因的定位可能为该疾病的早期准确诊断提供首个客观方法。在排除了整个人类基因组的45%后，我们研究了14个患有FMF的亚美尼亚家族和9个非阿什肯纳齐犹太家族，并测试了与16号染色体上α-珠蛋白基因座的连锁关系。对3'HVR（高变区）探针的PvuII长度多态性分析显示与FMF基因有显著连锁关系（在最大重组率[θ]=0.076时，最大对数优势分数[lodmax]=9.76）。在亚美尼亚人中，在θ=0.10时，lodmax=3.61；对于非阿什肯纳齐犹太人，在θ=0.06时，lodmax=6.28。没有证据表明亚美尼亚人和非阿什肯纳齐犹太人之间（卡方=1.28；P=0.26）或任何一个种族群体内部（卡方=0.00；P=0.50）存在基因异质性。因此，在非阿什肯纳齐犹太人和亚美尼亚人中，FMF基因均与16号染色体短臂上的α-珠蛋白复合体连锁。
